Baldness is the partial or complete lack of hair in certain areas of the body, mostly the head. The degree and pattern of baldness can vary greatly among individuals. The most common cause of hair loss and hair thinning in humans is male pattern baldness also referred to as Androgenic alopecia. Variant forms of Androgenic alopecia also exist in both men and women. Androgenic alopecia and variants thereof are not life threatening conditions but they often cause mental stress. Androgenic alopecia also occurs in animals such as in chimpanzee and orangutans. In humans, this condition is characterized by hair lost in a well-defined pattern, beginning above both temples. Hair also thins at the crown of the head, eventually causing this area to become partially or completely bald, leaving only a rim of hair around the sides and rear of the head. Baldness occurs more frequently in men and is especially more prevalent with advancing age. Baldness is less frequently observed in women. Although classic male pattern baldness or Androgenic alopecia rarely occurs in women, other variants of this condition where the hair becomes thinner around the whole scalp, but without the hairline receding, are observed in women.
Overall, baldness is considered undesirable from a cosmetic and aesthetic standpoint for both men and women. Therefore, considerable efforts have been devoted to combat baldness including, for instance, therapies aimed at lowering stress (cortisol) levels, hormonal therapy (e.g. 5α-reductase inhibitors), immunosuppressant therapy, and cosmetic procedures, such as hair transplant procedures.
Early hair transplant procedures consisted of removing hairs from a donor region covered with hair and transplanting donor hairs in a bald area. One of the donor areas often chosen for such procedure is the back of the head since hairs growing in this region are usually insensitive to Androgenic alopecia and variants thereof or other forms of baldness. During such procedures, donor hair along with a relatively large part of the skin surrounding the donor hair is harvested, and then transplanted in a suitable recipient area. Although the transplanted hairs settle relatively well at the transplant area and eventually become permanent with normal growth cycle, such method is far from being optimal. Specifically, one of the major disadvantages of this method is that not only the hairs removed from the donor region will never grow again but also the esthetic results obtained after hair transplant are disappointing for lack of realistic appearance. That is because of the relatively large size of the graft (hair plugs) requiring large puncture size for receiving the graft, and the poor hair density per hair implant. Furthermore, the issues related to the low hair density achieved by these method is difficult to counteract since only a limited amount of hair transplant (hair plugs) can be performed during a given surgical procedure. In sum, such hair transplantation technique offers very limited possibilities and is not “patient-friendly”.
Different hair transplant techniques have also been developed in an effort to improve the issues discussed above, and include methods for in vitro reproduction of hair or hair cloning. Such methods exploit the characteristics of the hair follicle. The essential growth structures of hair are the hair follicles, which contain hair follicular stem cells responsible for the growth of a new hair. The hair follicles also produce hair follicle cells or keratinocytes. During their journey to the surface of the skin, the cytoplasm of the hair follicle cells undergoes a large number of complex processes, which ultimately lead to the production of the tough and elastic material known as hair. The growth cycle of hair can be subdivided into three phases including the anagen phase (‘growth phase’), the catagen phase (‘transitional phase’), and the telogen phase (‘death phase’). The hair follicle plays a unique role in the cyclic nature of hair formation and hair growth, since it is the only part of the body that has the ability to completely regenerate (i.e. produce a new hair) after its removal from the body. This knowledge has been tested in vitro where it has been shown that hair follicle cells from plucked human hair can be cultured outside the body. It is also known that it is possible to use such cultured cells to form a differentiated epidermis or a fully developed epidermis, both in vitro and in vivo. Cultured hair follicle cells from mice can stimulate hair growth when said cells are implanted into test animals.
A hair transplant method exploiting this concept has been disclosed in European Patent Application 0236 014, in which epidermal follicle cells of the desired hair type are removed from the scalp skin of a donor subject. The epidermal follicle cells are then cultured in a culture medium, which preferably contains growth factors. In a subsequent step, a opening is made in the epidermis of the patients scalp and, via said opening, the cultured epidermal follicle cells are introduced/injected into the dermis next to the epidermis. Although an improvement over the more crude hair transplant method discussed above, the disadvantage of this method is that it is a very invasive procedure and that epidermal follicle cells cannot easily be placed in a targeted manner (i.e. to achieve a specific growth direction) on the scalp or other facial areas. In addition to that, the probability that the injected epidermal follicle cells will regenerate into the recipient region is rather low and as a result, large amount of epidermal follicle cells are required to increase the likelihood of survival. This represents an important limiting factor since such cells are not easily obtained and are difficult to culture in vitro.
Another hair transplantation method relying on the concept of hair multiplication has been described in European patent application 0 971 679. In this method, the donor hair in the anagen phase is removed from a donor area in such a way that the growth of a new hair (to replace the plucked hair), is enabled in the donor area. This method can be used to produce a new hair from the hair follicle stern cells obtained from the harvested hair. However, for this technique to succeed, the hair follicle stem cells must be cultured for long periods (ranging from 1 hour to 40 days, in a serum-free keratinocyte culture medium) before the donor hair can be implanted in the recipient area and produce a new hair. Therefore a main disadvantage of this method is the long time needed for culturing the hair follicle stem cells, causing inconveniency to the recipient subject, who must return to the clinic frequently in order to finalize the procedure. This is costly, time-consuming, and not “patient-friendly”. A refinement of this method has been described in European patent application 1957092. Although the time needed for culturing the hair follicle stem cells was greatly shorten, the esthetic results obtained still remain suboptimal since only a low density of hair can be achieved per hair transplant unit, i.e. only one new hair can be produced from the implanted donor hair (1 to 2 gain).
However, there is still a great need for improved hair transplantation methods relying on the concept of hair multiplication but where the aesthetic results obtained are more realistic and more natural looking. This may be achieved by increasing hair density per hair transplant unit in the recipient area. It is a goal of the present invention to provide an improved in vivo hair multiplication method, particularly to increase the hair density per hair transplant unit.